Surfactants, Preferably Used in the Manufacture of Pharmaceuticals and/or Cosmetics

The classification given below is a modified version of a review presented by L. O. de Guertechin (in G. Broze, Handbook of Detergents (Surfactant Series Vol. 82), Part A: Properties, pp. 7–46, Marcel Dekker Inc., New York and Basel 1999).

1 Anionic Surfactants

1.1 Salts and Esters of Carboxylic Acids

Free fatty acids are not used as surfactants, due to their low water solubility. However water-soluble fatty acid salts like alkali and short-chain amine salts (ethanol amine, diethanol amine, triethanol amine) show good water aﬃnity and are widely used. Saturated sodium soaps are extremely soluble in water up to C8 (these are not yet true surfactants); they become less soluble up to C18 (i.e., the domain of effective surfactants) and insoluble above C20. The fatty acids can be either saturated or unsaturated, starting from C16chain lengths. Unsaturated fatty acids are prone to undergo oxidation and form oxides and peroxides which cause rancidity and yellowing. Potassium soaps and salts of alkanolamines are more ﬂuid and also more soluble than sodium salts.

Fatty acid alkali salts (R = C7H15 −C17H35)

Fatty acid earth alkali salts (R = C7H15 −C17H35)

Fatty acid ethanol amine salts (R = C7H15 −C17H35)

Fatty acid isopropanol amine salts (R = C7H15 −C17H35)

Applications.

The main application of fatty acid salts is found in the soap bars used worldwide for hand-washing fabrics (generally based on tallow/coconut oil mixtures). Water-soluble soaps are mainly used in skin cleansers (soap bars or liquids), shaving products (sticks, foams, or creams), and deodorant sticks. Water-insoluble soaps form gels in nonaqueous systems and, due to their hydrophobicity, they can be appropriate surfactants or thickeners for w/o emulsions. Some of them are used as lubricants (e.g. magnesium stearate and calcium arachinate).

1.1.2 Ester Carboxylic Acids

They are monoesters of di- and tricarboxylic acids. These esters are produced by condensation reactions involving different types of molecules: either an alcohol with a polycarboxylic acid (e.g., tartaric or citric acid), or an hydroxyacid (e.g., lactic acid or citric acid) with a carboxylic acid. The alcohol may have been previously ethoxylated to enhance water solubility and surface activity.

Sodium dilaureth-7-citrate

Stearoyl disodium tartrate

Applications.

Due to their good foaming properties and substantivity on the hair, ester carboxylates are especially suitable in shampoos; in combination with alcohol ethoxy sulfates, they reduce skin irritation.

1.1.3 Ether Carboxylic Acids

These surfactants are formed by the reaction of sodium chloracetate with ethoxylated alcohols. Due to the addition of ethoxylated groups, ether carboxylates are more soluble in water and less sensitive to water hardness compared to conventional soaps. Also, keeping the best properties of nonionic surfactants, they do not exhibit any cloud point and show good wetting and foam stability. Ether carboxylates do not undergo hydrolysis in the presence of alkalis or acids.

Alkyl polyglycol ether carboxylate, sodium salt (R = C8H17 −C18H37)

Applications.

Emulsifiers and emulsion stabilizers, in hair conditioners and in shampoos in combination with alcohol ether sulfates and possibly with cationics.

1.2 Sulfuric Acid Derivatives

1.2.1 Alkyl Sulfates

Alkyl sulfates are organic esters of sulfuric acid; the sulfur atom is bridged to the carbon atom of the hydrocarbon chain via an oxygen atom. Sodium lauryl sulfate (SLS), one of the most common surfactants, belongs to this class.

Sodium alkylsulfate (Ropt. = C12H25 −C14H29)

Ammonium alkylsulfate (Ropt. = C12H25 −C14H29)

Monoethanol amine alkylsulfate (Ropt. = C12H25 −C14H29)

Applications.

Alkyl sulfates have been, for about 25 years, the most important synthetic surfactant. They are foamers, emulsifiers and are still used in cosmetics and personal care areas. They are also used in combination with other surfactants to improve the foaming characteristics of detergent systems. Pure SLS is used in oral care and incorporated in dental creams.

1.2.2 Alkyl Ether Sulfates

Alkyl ether sulfates (AES), which are also called alcohol ethoxy sulfates (AEOS), result from the sulfation of an ethoxylated alcohol.

1.3 Sulfonic Acids and Salts

In contrast to alkyl sulfates in alkyl sulfonates the sulfur atom is directly linked to the carbon atom making the substances stable against hydrolysis.

1.3.1 Alkyl Sulfonates

Three major types of alkyl sulfonates must be considered: the primary and secondary paraﬃn sulfonates (PS and SAS) and the α-olefin sulfonates (AOS).

Primary sodium alkyl sulfonate

Secondary sodium alkyl sulfonate

Sodium alkene sulfonate

Sodium hydroxy alkane sulfonate

Applications.

Alkane sulfonates (PS and SAS) are very water soluble showing good foaming, wetting and emulsifying properties. They are mainly used in Europe in heavy- and light-duty powder detergents as well as in all-purpose hard-surface liquid cleaners. Due to their excellent resistance to high electrolyte contents, alkane sulfonates have also found interesting prospects in concentrated industrial or domestic cleaners containing mineral chemical additives.

α-Olefin sulfonates have been mainly used in Asia as surfactants for heavy- and light-duty laundry detergents, synthetic soap bars, and household products; they have also been used in the United States in several personal care products (liquid soaps, bubble baths, and shampoos) as alternatives to alcohol ether sulfates. They are also marginally used in oral care formulations.

1.3.2 Alkyl Aryl Sulfonates

Linear alkylbenzene sulfonates are the most important surfactants used. They are biodegradable. Linear alkylbenzene sulfonates exhibit good chemical and thermal stabilities and can be incorporated in spray-dried slurries.

Sodium linear alkylbenzene sulfonate (LAS) (R = C9H19 −C15H31)

Applications.

Linear alkylbenzene sulfonates are very cost-effective surfactants which are used in a broad variety of detergents for household, fabric care, institutional, and industrial products. In laundry products (powders and liquids), LAS is the surfactant of choice, usually used in combination with other anionic or non-ionic surfactants. LAS is also an appropriate anionic surfactant for light-duty and delicate powder laundry detergents. Linear alkylbenzene sulfonates are wellknown in hand dishwashing formulations, often in combination with AEOS (i.e., alcohol ethoxy sulfate), providing better foam resistance. Due to its very high detersive action, LAS has a low compatibility with skin and is scarcely used in cosmetics, except in antiseborrheic preparations.

1.3.3 Sulfosuccinates

Sulfosuccinates are the sodium salts of alkyl esters of sulfosuccinic acid; monoesters of sulfosuccinic acid based on linear fatty alcohols are only partially water-soluble and hardly dispersible. Those based on fatty alcohol ethoxylates exhibit much better solubility. Dialkyl esters based on alcohols with less than nine carbons, preferably five to eight carbon atoms, as well as those based on fatty acid ethanol amides are water soluble and, therefore, are generally preferred. Disodium salts of monoesters deliver good detergency and foam properties. Due to the ester linkage, all sulfosuccinates are sensitive to hydrolysis, especially under acidic conditions.

Sodium dialkyl sulfosuccinate

Sodium alkyl sulfosuccinamate

Sodium ethoxylated alkylamido sulfosuccinate

Applications.

The monoesters of alkanolamides and their derivatives are extensively used in personal care products and especially in shampoos often in combination with other anionic surfactants. The diesters are used as dispersing and wetting agents in industrial or institutional applications such as emulsion polymerization, the textile industry, ink manufacture, dry cleaning, and agriculture.

1.3.4 Sulfo Fatty Acid Esters

Among this group of surfactants the α-sulfo fatty acid esters are commonly used on an industrial scale. The α-sulfo fatty acid esters contain the sulfonate group statistically distributed along the carboxylate chain.

Applications.

Taurides (or taurates) are acylamino alkane sulfonates which have chemical structures close to isethionates.

Fatty acid isethionate

Tauride

Applications.

These surfactants are insensitive to water hardness and show good wetting, foaming, and emulsifying properties. In addition, they have excellent compatibility with the skin. Acyl isethionates have been used in shampoos and personal cleaners. They are also incorporated in syndet bars, together with various soaps.

1.4 Phosphoric Acid Esters and Salts

This class of surfactants includes alkyl phosphates and alkyl ether phosphates.

Disodium alkyl phosphoric ester

Sodium dialkyl phosphoric ester

Sodium ethoxylated alkyl phosphate

Sodium di-ethoxylated alkyl phosphate

Applications.

Phosphate esters are used in formulations where a particular tolerance to pH, heat, or electrolytes is required. They are also used in acidic cleaning products for household as well as industrial applications. They act as metal stripping or dipping agents and, thereby, increase paint adhesion. The phosphate esters also show antistatic properties to the treated substrates. Incorporated in dry cleaning compositions, phosphate ester provide, in addition to an exceptional detergency. The less water-soluble phosphate esters are also used as antifoaming agents and are applied as emulsifiers in agrochemical applications (e.g., concentrate fertilizer solutions).

1.5 Acylamino Acids and Salts

1.5.1 Acyl Glutamtes

Acyl glutamtes are based on α-aminoglutaric acid.

HOOC−CH2−CH2−CH(NH2)−COOH

α-aminoglutaric acid

Sodium acylglutamate

Applications.

Personal care products such as shampoos, mild to the skin and delivering improved skin feel.

1.5.3 Acyl Sarcosides

Applications.

Sarcosinates are mild to skin. They are also used as corrosion inhibitors.

2 Cationic Surfactants

2.1 Alkyl Amines

Primary, secondary, and tertiary alkyl amines and, especially, their salts are uncharged in neutral solution and therefore are not strictly cationic. They can be considered as cationics in a pH low enough to provide the ionic form; otherwise, they must be considered as nonionics. Salts of fatty amines can deliver a germicidal activity; their fungicidal eﬃcacy is enhanced when the amine is neutralized with salicylic or o-chlorobenzoic acid.

Alkyl amine salt

Dimethyl alkyl amine salt

Alkylamido dimethyl propylamnine salt

Applications.

Amines are used in textile treatment (e.g., antistatic treatment) and occasionally in rinse fabric softeners. Amido-amines are also used in cosmetic products. Salts of stearyl and tallow fatty amines are used in some mining applications (e.g., ﬂotation process). Fatty amines, diamines and polyamines find other prospects as adhesive agents in the coating of damp surfaces with paint or bitumen and as corrosion inhibitors.

2.2 Alkylimidazolines

Alkyl aminoethyl imidazoline

Alkyl hydroxyethyl imidazoline

Imidazolines are cationic O/W emulsifiers. They adsorb at metal surfaces and improve the adhesion of the applied layer to substrates.

2.3 Quaternary Ammonium Compounds

2.3.1 Tetraalkyl(-aryl) Ammonium Salts

The water solubility of quaternaries primarily depends on the nature of R substituents (hydrophobic chain lengths, polarity, etc.). Quaternaries carrying two or more long hydrophobic chains have very poor water solubility. Low-solubility quaternaries can adsorb on various substrates and impart various useful conditioning effects (softening, antistatic, corrosion inhibition, etc.). Quaternaries are generally not compatible with anionics because of the formation of a water-insoluble complex.

Applications.

The major use of quarternaries is related to their ability to adsorb on natural or synthetic substrates and fibers. Less-soluble long hydrophobic chain containing compounds (e.g., C16-C18 dialkyldimethyl ammonium chlorides) deposit on fibers. Their softening and antistatic properties are similarly exploited in hair conditioning shampoos or after-shampooing rinses. In cosmetic applications, quaternaries could cause ocular and local irritation; nevertheless, their potential for skin penetration is very low. Among the quaternaries, some are used as germicides, disinfectants, or sanitizers, they are especially effective against gram-positive but less effective against gram-negative bacteria. Quaternaries are also used as emulsifiers in acidic creams and lotions. N-Alkyltrimethyl ammonium salts are used as emulsifiers in applications requiring a selective adsorption of the emulsifier on the treated substrate.

2.3.2 Heterocyclic Ammonium Salts

Heterocyclic quaternaries are derived from heterocyclic aliphatic or aromatic compounds. They are often based on morpholine, imidazoline, pyridine and isoquinoline.

Alkylethyl morpholinium ethosulfate

Alkylpyridinium chloride

Dialkylmethyl imidazolinium methosulfate

Applications.

The quaternaries derived from imidazoline and morpholine are used as hair conditioners and antistatic agents. Those derived from aromatic heterocycles are used as germicides. N-Alkyl imidazoline chlorides are also used as emulsifiers in applications where the adsorption of the emulsifying agent on the substrate is desired.

2.4 Ethoxylated Alkyl Amines

These surfactants can be considered as cationic or nonionic, depending on the degree of ethoxylation and on the pH at which they are used. Polyethoxylated amines are formed by ethoxylation of primary or secondary fatty amines. The poloxamines are formed by the reaction of ethylene diamine with propylene oxide. Other tetrafunctional products are obtained by successive reactions of ethylene diamine with ethylene oxide and propylene oxide. lt must be noted that the above surfactants based on ethylene diamine, although intrinsically cationic, essentially behave as nonionic surfactants.

Applications.

Amphoterics of this class are similar to those of betaines. They are used in personal care products, baby shampoos, fabric softeners, industrial and car cleaners. They are compatible with other surfactants and tolerate hard water and electrolytes.

3.2 N-Alkyl Amino Acids or Imino Diacids

These molecules are chemical derivatives of amino acids.

Alkyl aminopropionic acid sodium salt

Sodium coco glycinate

Di-carboxyethyl-alkylamin disodium salt

Applications.

N-Alkyl amino acids or diacid amphoterics are used in personal care household products. They are compatible with other surfactants, electrolytes and hard water. They show good emulsifying, foaming and wetting properties.

The positive charge is always carried by a quaterized nitrogen, whereas the anionic site can be a carboxylate (betaine), a sulfate or a phosphate. Betaines are good foaming, wetting, and emulsifying surfactants, especially in the presence of anionics. Detergency is best in alkaline conditions. Betaines are compatible with other surfactants and they frequently form mixed micelles; these mixtures often deliver unique properties which are not found in the individual constitutive surfactants. In their straight cationic form (i.e., in neutral and acidic conditions), betaines are not affected by water hardness ions and other metallic ions. They have hydrotropic properties, helping to solubilize ethoxylated nonionic surfactants in the presence of salting-out ions. Betaines are especially mild to skin and have the ability to improve the skin tolerance against irritating anionic surfactants.

Alkylbetaine

Alkylamidopropyl betaine

Imidazolinium betaine

Alkylamidopropyl hydroxysultaine

Alkylamidopropyl hydroxyphostaine

Applications.

Betaines have low eye and skin irritation; moreover, the presence of betaines is known to decrease the irritation effect of anionics. For the above reasons and also due to their high price, they are usually used in association with other surfactants. Betaines are thus especially suitable in personal care applications (shampoos, foam baths, liquid soaps, shower gels, etc.), fabric hand-wash products, and dish-washing products.

4 Nonionic Surfactants

4.1 Fatty Alcohols

Applications.

Fatty alcohols are primarily used as co-emulsifiers. They are starting materials in the production of ethoxylated fatty alcohols.

4.2 Ethers

4.2.1 Ethoxylated Fatty Alcohols

There is a wide range of emulsifiers, wetting agents and solubilizers based on fatty alcohols available. They vary in both: the chain length of the fatty alcohol and the ethoxyl content. The inﬂuence of the fatty alcohol chain length on the properties of the compound is small compared to that of the polyoxyethylene chain.

Fatty alcohol polyglycol etherwith x = C8 −C18 and y =∼ 2 to 300

Applications.

Detergents in industrial and household products often in combination with nonionics. Ethoxylated fatty alcohols are also used in personal care products as emulsifiers and solubilizers.

These surfactants consist of a central polypropylene glycol part (PPG) representing the hydrophobic portion of the molecule and two hydrophilic polyethylene glycol chains (PEG). They are also called EO/PO block polymers. Depending on the mol weight and the proportion between PPG and PEG a wide variety of surface active agents can be produced, showing different properties.

Applications.

EO/PO block polymers are used in dishwashing and laundry detergents. They have thickening and gelling properties which makes them interesting for cosmetics. In the pharmaceutical field the more hydrophilic types are used as solubilizers under the name poloxamer.

4.2.3 Alkylphenol Ethoxylates

They are also called alkylphenol polyglycol ethers and belong to the most important types of washing active substances with excellent wetting properties. Due to ecotoxicological reasons their use however diminishs. The octylphenol and nonylphenol ethers are of special importance.

Applications.

The numerous hydroxyls of glucoside groups ensure the solubility of the whole molecule in water. Alkylpolyglucosides (APGs) show good water solubility and have their cloud points at rather high temperatures (generally above 100℃); they are only slightly sensitive to the presence of electrolytes and are only very rarely inﬂuenced by water hardness. The optimal detergency of APGs is found for an average alkyl chain length around 13 and a glucosidic content of about 65 %. Alkylpolyglucosides show good chemical stability at neutral and alkaline pH. Their biodegradability is excellent.

AlkylpolyglucosideR = fatty acid

Applications.

Alkylpolyglucosides are used in detergents and personal care cleansers (e.g., shampoos); they are known to be mild for skin.

Applications.

Ethoxylated products of lanolin and castor oil are good emulsifiers and solubilizers respectively. They are mainly used in the cosmetics industry; the ricinus based products are solubilizers for pharmaceutical purposes.

4.3 Alkanolamides

4.3.1 Alkanolamides

Alkanolamides are N-acyl derivatives of monoethanolamine and diethanolamine.

Monoalkanolamide

Dialkanolamide

Esteramide

Applications.

Alkanolamides are foamers, foam boosters and foam stabilizers. They are used in household detergent products, shampoos and cleaners.

4.3.2 Ethoxylated Alkanolamides

The reaction of an alkanolamide with ethylene oxide leads to an ethoxylated amide. Their properties are comparable to those of ethoxylated alcohols.

Polyethoxylated monoalkanolamide

Polyethoxylated dialkanolamide

Applications.

As thickening, foam stabilizing and dispersing substances. Their application in car wash is also mentioned.

4.4 Esters

4.4.1 Ethoxylated fatty acids

Theoretically POE could react at both ends with one fatty acid. Nevertheless the reaction of a fatty acid with ethylene oxide leads mainly to the monoester with a broad distribution in the molar EO number (n); the reaction of polyethylene glycol with fatty acids leads to a mixture of mono- and diesters besides free fatty acid.

Fatty acid monoester

Fatty acid diester

The monoesters are much more soluble in water than the diesters. These surfactants are readily hydrolyzed under acidic or alkaline conditions.

Applications.

If properly balanced, combinations of esters with low and high degree of ethoxylation provide excellent emulsifier properties for creams and lotions. Therefore they have special interest in combined emulsifiers in pharmacy.

Applications.

Due to their very low toxicity, these surfactants are edible and, therefore, they are widely used in the food industry, especially in applications involving W/O emulsions or dispersions (e.g., butter, diet butter, margarine, etc.). Glycol and glycerol esters are also used in pharmaceutical and cosmetic industry either as emulsifying agents or as oily compounds in creams, lotions, ointments, gels.

Sorbitol can form two different sorbitans by internal dehydration: the 1,4- and the 1,5-sorbitan. Further dehydration of the 1,4-sorbitan leads to iso-sorbide. In common sorbitan based surfactants the 1,4-sorbitan is dominating. Fatty acid esters of sorbitan are insoluble in water, their HLB value is below 10.

Applications.

Emulsifiers often in combination with ethoxylated sorbitanesters of fatty acids.

4.4.4 Alkyl Carbohydrate Esters

Alkyl carbohydrate esters are also known under the names ”sugar esters” and”sucrose esters”. Normally they ar based on saccharose. Mono- and diesters are produced. The mono esters are water soluble while the dieseters are not. Due to the steric effects, primary hydroxyl groups are almost exclusively subject to esterification. They are of great interest due to their natural origin of their components and good biodegradability.

Applications.

These surfactants contain besides the ester group, which is formed by a fatty acid and a polyol as described in the previous section, ether linkages normally originating from polyoxyethylene. In general they are more hydrophilic compared to the ester surfactants and exhibit HLB values above 10.

Applications.

4.5.4 Polyglycerol monoester

This is the only class of ether bounds containing emulsifiers which do not contain polyoxyethylene groups. The ether linkage is formed from glycerol units.

Polyglycerol monoleate

4.6 Amine Oxides

Amine oxides are produced from alkyl dimethyl amine, where the alkyl chain is a C12-C18 unit by oxidation. The methyl groups could be partially replaced by other functional groups like amidopropyl, hydroxyethyl or hydroxypropyl.

Applications.

These surfactants are used as additives in paints, foam controlling agents, textile auxiliaries, wetting agents and in cosmetic preparations like protectic creams, body milks, shampoos and conditioners.

6 Fluorosurfactants

Fluorosurfactants contain perﬂuoroalkyls chains F-(CF2-CF2)-, in which n ranges from about 3 to about 8. They are excellent wetting agents showing a critical surface tension of about 25mN/m. Similar to conventional surfactants, a rather broad variety of hydrophilic functions (ethoxylated chains, sulfonates, quaternaries, betaines, etc.) can be born by ﬂuorosurfactants. These hydrophilic groups are generally not directly grafted on the ﬂuorocarbon chain and are linked through a short intermediate hydrocarbon chain. Depending on their nature, these surfactants show variable emulsifying and foaming characteristics. They have excellent thermal and chemical stability; therefore, they find prospects in those extreme conditions in which the hydrocarbon surfactants would decompose. The major drawback of ﬂuorosurfactants is that they are not environment friendly because they are resistant to biodegradation.

Applications.

Although they have some potential prospects in personal care (improved hair conditioning) and household, ﬂuorosurfactants find their major applications in industrial areas like water based adhesives, wetting agents, ﬂotation processes and battery technology.